This document discusses tests used to evaluate renal function, including estimates of glomerular filtration rate (GFR) using serum creatinine, BUN, eGFR formulas, and creatinine clearance tests. It describes the production and handling of creatinine by the kidneys and limitations of eGFR estimates. The document also covers urinalysis components like urine color, specific gravity, protein, and sediment analysis and what various findings indicate about kidney conditions.

1. Tests of Renal Function
Cyrus Cryst MD FASN
VMMC

2. Estimates of Glomerular function
• Serum Creatinine
• BUN
• eGFR
• Cockroft-Gault Formula or MDRD
• 24 hour Creatinine Clearance
• Iothalamate Clearance

3. Plasma Creatinine
• Creatinine is derived from metabolism of creatine
in skeletal muscle and in dietary meat protein
• It is released constantly into the circulation
• It is freely filtered at the glomerulus and is neither
absorbed nor metabolized by the kidney
• 15% of urinary creatinine is derived from tubular
secretion

4. Plasma Creatinine
• GFR x PCr = Ucr x Volume
• GFR = Ucr x Volume / PCr
• This formula overestimates the true GFR by
10-15% (due to tubular secretion of
creatinine) and that is balanced by the error
in creatinine measurement.

5. Calculation of CCR
• If : PCr = 1.2 GFR = U V/P
• Ucr = 100 mg/dl
• V = 1.2 Liters per day
• GFR = 100 mg/dl x 1.2mg/dl /1.2L/day= 100 L/day
• This must be multiplied by 1000 ml/liter and again by
1/1440 (minutes per day) To yield conventional units:
70 ml/min
Normal is 130 ml/min in men and 120 ml/min
in women

6. Limitations of eGFR
• Only applies in “steady state”
• Only for those with impaired GFR < 60
• Only for those under 65
• Depends on accurate measurement of creat
• CKD-EPI formula for “normal population”

7. Plasma Creatinine
• Is the most useful
blood test to monitor
change in renal
function.
• Change in plasma
creatinine means a
change in rate of
production OR a
change in GFR
• Don’t neglect
conditions that cause
increase in plasma
creatinine production:
– Rhabdomyalysis
– Protein ingestion
• Drugs affect creatinine
secretion can raise
creat 10% (trimethaprim)

8. eGFR to Creat

9. eGFR and Creatinine
• Nomogram – takes creat and ‘assigns’ an
estimate of GFR
• No account of age, muscle mass, prior
condition – two values for race.
• Very concerning for patients to be told “stage 3
kidney failure”
• No context can go up and down
• At extremes of age, weight, muscle mass may
be inaccurate

10. Heat map: stages of renal
impairment

11. When Creatinine Elevation is
Misleading
• Pts who have lost or donated a kidney
• People taking sulfa-TRIMETHOPRIM
• Volume depletion – ‘fasting’
• ACEI and ARB – lead to ~30% decline in
eGFR that is reversible with discontinuation
of the drug

12. Clinical tips
• A plasma creatinine rising 1.0 mg/dl/24
hours reflects GFR = 0
• RAAS inhibitors can raise serum creat by
0.2-0.6 depending on volume depletion
• Getting a complete 24 hour urine for Creat
Clearance in the hospital is very difficult.

13. Urinalysis in renal disease
• Color
• Specific Gravity
• Leucocyte Esterase
• Protein
• pH
• Osmolality
• Glucose
• Part 2
– Sediment
– Patterns of injury
• Part 3
– Urine electrolytes
– Settings where useful

14. Urine Color
• Usually clear, light yellow
• Lighter when dilute, darker when concentrated
• White due to phosphate crystals or pyuria
• Green due to methylene blue dye, propofol
• Black due to malignancy
• Red or brown due to Heme or pigments
• Turbidity may indicate infection, crystals or
phosphates

15. Red urine
• Hematuria - the sediment is red, supernatent
is clear
• If supernatent is RED, test for heme.
– Heme Positive - RHABDOMYALYSIS
– Heme Negative? - RARE- Porphyuria, Beets,
phenazopyridine.

17. Urine Specific Gravity
• Surrogate for urine osmolality
• Indicates dilute or concentrated urine
• SG of 1.010 is about isosomolar
• Highest in extreme vol depletion 1.030
• May be falsely high in cases of contrast
excretion or glucose
• Cannot be falsely low

18. Leucocyte Esterase
• Enzyme released by neutrophils – marker for
leucocytes in urine.
• False positive if urine is VERY dilute or
concentrated
• False Negative if urine is very concentrated
• Nitrates- test for presence of nitrate reductase
– Also has false pos, negs and not elaborated by all bugs

19. Leucocyte Esterase
• Leukocyte estrase and nitrite - surrogate
markers for pyuria and enterobacteriaceae
• Postive results may be an important clue:
– May detect WBC or bacteria not associated with UTI!
– “sterile pyuria?”
• TB,
• Interstitial nephritis,
• Stones

20. Urine Protein
• Patients usually only excrete 150 mg
protein /day or less
• Dipstick usually only picks up ALBUMIN
• Dipstick usually positive only for >300
mg/day
• Scores 1-2-3+
• Sulfosalicylic acid test - for light chains

21. Microalbuminuria
• Screening test for diabetic nephropathy
• Risk factor for cardiac disease
• Also used with microalbumin/creat ratio

22. Quantitative protein excretion
• 24 hour collection determines if patient has
“nephrotic range” proteinuria - evidence of
glomerular disease - >3.5 gm/1.73 M2
• Alternative method is to use a spot Protein-
to-creatinine ratio in mg/mg which
correlates with g/1.73 M2
protein excretion.

23. Urine pH
• Range is 4.5-8.0
• Best use is in Metabolic acidosis - normally
patients should excrete an acid urine pH <5
– If urine pH is >5 In a patient with ACIDOSIS
suspect a renal tubular acidosis
– If urine pH is > 7.0 - 9.0 - suspect a urease
producing organism such as P. miriabilis
(associated with staghorn calculi)

24. Urine Osmolality
• Plasma osmolality is maintained in a narrow range
normally by the kidney’s ability to elaborate urine
that varies widely in osmolality.
• Urine osmolality measurements are key to
unraveling the DDX of
• hypernatremia,
• hyponatremia,
• polyuria

25. Urine Glucose
• Indicates High plasma glucose levels (but is
insensitive)
• Can indicate a proximal tubular
reabsorptive problem - Fanconi’s syndrome
• Urinary glucose measurements reflect mean
glucose levels, not peak concentrations.

26. PART II
• The Urine Sediment Exam

28. Sediment
• Crystals
• Cells
– Heme
– Wbc
– epithelial
• Bacteria
• Casts
• Patterns

29. Crystals
• Uric Acid
• Calcium
• Cystine
• Struvite - magnesium/ammonium/phosphate

31. Crystals

33. Sediment - Cells
• Pyuria
– May reflect infection
– Usually accompanies any renal disease
– May be stained for eosinophils
• Tubular epithelial cells
– In casts reflect ATN
– Individually are seen in many situations

35. Sediment - Cells
• Hematuria -
– Always abnormal in older men
– Can be transient in younger patients
– RBC morphology can reflect upper or lower
tract bleeding
– Persistent heme needs to be evaluated
– Always present if foley in place

38. Urine sediment - Casts
• Hyaline
• Red Cell Casts
• WBC casts
• Epithelial cell casts
• Fatty casts
• Granular cell casts
– Muddy brown casts
• Waxy casts
• Broad casts

43. Urine sediment patterns
• Hematuria, >3.5 grams of protein a day,
RBC casts, dysmorphic red cells, and
Lipiduria
– Any of these findings singly or in combination
reflect glomerular disease, or vasculitis

44. Urine sediment patterns
• Multiple granular and epithelial cell casts
with free epithelial cells.
– Coarse granular casts in “dirty” background
– Signifies ATN - acute toxic or ischemic injury
– Beware of hyperbilirubinemia

46. Urine sediment patterns
• Pyuria with WBC and Granular or waxy
casts and no proteinuria
– Suggests interstitial disease or Obstruction
– Can be seen with other signs of glomerular
disease

47. Urine sediment patterns
• Hematuria alone
– Variable significance - depends on the setting
• Stone? Flank pain
• Tumor? Age, imaging studies
• Mild glomerular disease - IgA, thin basement
membrane disease, Alport’s,
• PCKD

48. Urine sediment patterns
• Hematuria and Pyuria with no or variable
casts-can be seen with any of the following:
– Interstitial nephritis
– Glomerular disease
– Vasculitis
– Obstruction
– Renal infarction

49. Urine sediment patterns
• Pyuria alone?
• Usually a UTI
• Sterile pyuria suggests TB, analgesic nephropathy

51. Tests of renal function
Part 3 - Urine Electrolytes
• Sodium excretion
• FENa
• Chloride excretion
• Potassium excretion
• Urine osmolality and pH